Genetic Variant NM_001195234.1:c.702C>G (chr11-90037943-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001195234.1(TRIM49C):c.702C>G(p.Asn234Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 5)

Exomes 𝑓: 0.00018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49C
NM_001195234.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.184

Variant links:

Genes affected

TRIM49C (HGNC:38877): (tripartite motif containing 49C) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM49C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019607127).

BP6

Variant 11-90037943-C-G is Benign according to our data. Variant chr11-90037943-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2279782.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM49C	NM_001195234.1 link	c.702C>G	p.Asn234Lys	missense_variant	Exon 5 of 8	ENST00000448984.1	NP_001182163.1	P0CI26
TRIM49C	XM_024448656.2 link	c.702C>G	p.Asn234Lys	missense_variant	Exon 3 of 6		XP_024304424.1
TRIM49C	XM_017018126.2 link	c.508-750C>G		intron_variant	Intron 2 of 4		XP_016873615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM49C	ENST00000448984.1 link	c.702C>G	p.Asn234Lys	missense_variant	Exon 5 of 8	1	NM_001195234.1	ENSP00000388299.1		P0CI26

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

32728

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000551

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000212

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

6934

Hom.:

AF XY:

0.000259

AC XY:

AN XY:

3862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000704

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000185

AC:

AN:

243518

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

AN XY:

125346

show subpopulations

Gnomad4 AFR exome

AF:

0.000194

Gnomad4 AMR exome

AF:

0.000197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000305

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.000168

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000214

AC:

AN:

32728

Hom.:

Cov.:

AF XY:

0.000138

AC XY:

AN XY:

14452

show subpopulations

Gnomad4 AFR

AF:

0.000266

Gnomad4 AMR

AF:

0.000551

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000212

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 25, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.12

DANN

Benign

0.094

DEOGEN2

Benign

0.0021

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.022

M_CAP

Benign

0.00044

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

1.9

REVEL

Benign

0.022

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.051

MutPred

0.47

Gain of ubiquitination at N234 (P = 0.0155);

MVP

0.014

MPC

1.9

ClinPred

0.023

GERP RS

1.1

Varity_R

0.027

gMVP

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over